Modulation of Macrophage Activation

Abstract

The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that modulate macrophage activation. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to modulate macrophage activation. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired potency to modulate macrophage activation.

1 - 13 . (canceled) 
     
     
         14 . A method for obtaining cells that have a desired potency for modulating macrophage activation, the method comprising assaying cells for the desired potency and selecting cells that have the desired potency, the cells being non-embryonic stem, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         15 . A method for treating inflammation in a subject having a condition, the method comprising administering the cells obtained by the method of  claim 14 , having the desired potency for modulating macrophage activation, to the subject in a therapeutically effective amount and for a time sufficient to achieve a therapeutic result. 
     
     
         16 . A method for treating inflammation in a subject having a condition, the method comprising administering the cells obtained by the method of  claim 14 , having the desired potency for modulating macrophage activation, to the subject in a therapeutically effective amount and for a time sufficient to treat inflammation so as to achieve a therapeutic result, wherein, prior to administration, the cells were validated as having the desired potency. 
     
     
         17 . A method for modulating macrophage activation in a subject having a condition that can be treated by modulating macrophage activation, the method comprising administering the cells obtained by the method of  claim 14 , having the desired potency for modulating macrophage activation, to the subject in a therapeutically effective amount and for a time sufficient to modulate macrophage activation so as to achieve a therapeutic result. 
     
     
         18 . A method for modulating macrophage activation in a subject having a condition that can be treated by modulating macrophage activation, the method comprising administering the cells obtained by the method of  claim 14 , having the desired potency for modulating macrophage activation, to the subject in a therapeutically effective amount and for a time sufficient to modulate macrophage activation so as to achieve a therapeutic result, wherein, prior to administration, the cells were validated as having the desired potency. 
     
     
         19 . The method of  claim 15 , wherein the administered cells are allogeneic. 
     
     
         20 . The method of  claim 15 , wherein the administered cells increase neuroprotective (M2) and/or decrease neurotoxic (M1) activation. 
     
     
         21 . The method of  claim 14  wherein potency is assessed by an assay selected from the group consisting of (1) assay for macrophage activation factor expressed in or secreted by the cells, (2) assay for macrophage activation, (3) assay for antigen presentation of macrophages, and (4) assay for morphological changes of macrophages during activation. 
     
     
         22 . A method for determining a therapeutically effective amount of cells administered to a subject having a condition, the cells being non-embryonic stem, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1, and/or can differentiate into cell types of at least two of endodermal, ectodermal, or mesodermal germ layers, the method comprising assessing, following administration of the cells to the subject, an in vivo biomarker of activated macrophage in a subject in vivo, wherein the cells express and secrete one or more factors that modulate macrophage activation. 
     
     
         23 . The method of  claim 15 , wherein the condition is selected from the group consisting of acute and chronic conditions in central nervous system injury, e.g., stroke; ischemic stroke, multiple sclerosis, Alzheimer's Disease, ALS, Parkinson's Disease, hypoxic-ischemia, neonatal hypoxic ischemia, and traumatic brain or spinal cord injury. 
     
     
         24 . The method of  claim 15 , wherein the subject is human. 
     
     
         25 . A method for constructing a cell bank, the method comprising expanding and storing the cells obtained by the method of  claim 14  for future administration to a subject. 
     
     
         26 . A method for constructing a cell bank, the method comprising expanding and storing cells for future administration to a subject, the cells being non-embryonic stem, non-germ cells that express one or more of oct4, telomerase, rex-I, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers, the cells having been validated for having a desired potency for modulating macrophage activation. 
     
     
         27 . A method for drug discovery, the method comprising exposing the cells obtained by the method of  claim 14  to an agent to assess the effect of the agent on the ability of the cells to modulate macrophage activation.